Critical Reviews in Biochemistry and Molecular Biology最新文献

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Ribosome-associated quality control and CAT tailing. 核糖体相关质量控制和CAT尾尾。
IF 6.5 2区 生物学
Critical Reviews in Biochemistry and Molecular Biology Pub Date : 2021-12-01 Epub Date: 2021-07-07 DOI: 10.1080/10409238.2021.1938507
Conor J Howard, Adam Frost
{"title":"Ribosome-associated quality control and CAT tailing.","authors":"Conor J Howard,&nbsp;Adam Frost","doi":"10.1080/10409238.2021.1938507","DOIUrl":"https://doi.org/10.1080/10409238.2021.1938507","url":null,"abstract":"<p><p>Translation is the set of mechanisms by which ribosomes decode genetic messages as they synthesize polypeptides of a defined amino acid sequence. While the ribosome has been honed by evolution for high-fidelity translation, errors are inevitable. Aberrant mRNAs, mRNA structure, defective ribosomes, interactions between nascent proteins and the ribosomal exit tunnel, and insufficient cellular resources, including low tRNA levels, can lead to functionally irreversible stalls. Life thus depends on quality control mechanisms that detect, disassemble and recycle stalled translation intermediates. <u>R</u>ibosome-associated <u>Q</u>uality <u>C</u>ontrol (RQC) recognizes aberrant ribosome states and targets their potentially toxic polypeptides for degradation. Here we review recent advances in our understanding of RQC in bacteria, fungi, and metazoans. We focus in particular on an unusual modification made to the nascent chain known as a \"CAT tail\", or <u>C</u>arboxy-terminal <u>A</u>lanine and <u>T</u>hreonine tail, and the mechanisms by which ancient RQC proteins catalyze CAT-tail synthesis.</p>","PeriodicalId":10794,"journal":{"name":"Critical Reviews in Biochemistry and Molecular Biology","volume":" ","pages":"603-620"},"PeriodicalIF":6.5,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/10409238.2021.1938507","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39161370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 10
Isothermal amplifications - a comprehensive review on current methods. 等温扩增——对现有方法的综合评述。
IF 6.5 2区 生物学
Critical Reviews in Biochemistry and Molecular Biology Pub Date : 2021-12-01 Epub Date: 2021-07-15 DOI: 10.1080/10409238.2021.1937927
Jörn Glökler, Theam Soon Lim, Jeunice Ida, Marcus Frohme
{"title":"Isothermal amplifications - a comprehensive review on current methods.","authors":"Jörn Glökler,&nbsp;Theam Soon Lim,&nbsp;Jeunice Ida,&nbsp;Marcus Frohme","doi":"10.1080/10409238.2021.1937927","DOIUrl":"https://doi.org/10.1080/10409238.2021.1937927","url":null,"abstract":"<p><p>The introduction of nucleic acid amplification techniques has revolutionized the field of medical diagnostics in the last decade. The advent of PCR catalyzed the increasing application of DNA, not just for molecular cloning but also for molecular based diagnostics. Since the introduction of PCR, a deeper understanding of molecular mechanisms and enzymes involved in DNA/RNA replication has spurred the development of novel methods devoid of temperature cycling. Isothermal amplification methods have since been introduced utilizing different mechanisms, enzymes, and conditions. The ease with which isothermal amplification methods have allowed nucleic acid amplification to be carried out has had a profound impact on the way molecular diagnostics are being designed after the turn of the millennium. With all the advantages isothermal amplification brings, the issues or complications surrounding each method are heterogeneous making it difficult to identify the best approach for an end-user. This review pays special attention to the various isothermal amplification methods by classifying them based on the mechanistic characteristics which include reaction formats, amplification information, promoter, strand break, and refolding mechanisms. We would also compare the efficiencies and usefulness of each method while highlighting the potential applications and detection methods involved. This review will serve as an overall outlook on the journey and development of isothermal amplification methods as a whole.</p>","PeriodicalId":10794,"journal":{"name":"Critical Reviews in Biochemistry and Molecular Biology","volume":" ","pages":"543-586"},"PeriodicalIF":6.5,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/10409238.2021.1937927","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39188051","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 47
Mechanisms of hexameric helicases. 六聚体螺旋酶的机制。
IF 6.5 2区 生物学
Critical Reviews in Biochemistry and Molecular Biology Pub Date : 2021-12-01 Epub Date: 2021-08-17 DOI: 10.1080/10409238.2021.1954597
Amy J Fernandez, James M Berger
{"title":"Mechanisms of hexameric helicases.","authors":"Amy J Fernandez, James M Berger","doi":"10.1080/10409238.2021.1954597","DOIUrl":"10.1080/10409238.2021.1954597","url":null,"abstract":"<p><p>Ring-shaped hexameric helicases are essential motor proteins that separate duplex nucleic acid strands for DNA replication, recombination, and transcriptional regulation. Two evolutionarily distinct lineages of these enzymes, predicated on RecA and AAA+ ATPase folds, have been identified and characterized to date. Hexameric helicases couple NTP hydrolysis with conformational changes that move nucleic acid substrates through a central pore in the enzyme. How hexameric helicases productively engage client DNA or RNA segments and use successive rounds of NTPase activity to power translocation and unwinding have been longstanding questions in the field. Recent structural and biophysical findings are beginning to reveal commonalities in NTP hydrolysis and substrate translocation by diverse hexameric helicase families. Here, we review these molecular mechanisms and highlight aspects of their function that are yet to be understood.</p>","PeriodicalId":10794,"journal":{"name":"Critical Reviews in Biochemistry and Molecular Biology","volume":"56 6","pages":"621-639"},"PeriodicalIF":6.5,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9869668/pdf/nihms-1863989.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9159527","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Modular optimization in metabolic engineering. 代谢工程中的模块化优化。
IF 6.5 2区 生物学
Critical Reviews in Biochemistry and Molecular Biology Pub Date : 2021-12-01 Epub Date: 2021-06-27 DOI: 10.1080/10409238.2021.1937928
Matthew Wong, Abinaya Badri, Christopher Gasparis, Georges Belfort, Mattheos Koffas
{"title":"Modular optimization in metabolic engineering.","authors":"Matthew Wong,&nbsp;Abinaya Badri,&nbsp;Christopher Gasparis,&nbsp;Georges Belfort,&nbsp;Mattheos Koffas","doi":"10.1080/10409238.2021.1937928","DOIUrl":"https://doi.org/10.1080/10409238.2021.1937928","url":null,"abstract":"<p><p>There is an increasing demand for bioproducts produced by metabolically engineered microbes, such as pharmaceuticals, biofuels, biochemicals and other high value compounds. In order to meet this demand, modular optimization, the optimizing of subsections instead of the whole system, has been adopted to engineer cells to overproduce products. Research into modularity has focused on traditional approaches such as DNA, RNA, and protein-level modularity of intercellular machinery, by optimizing metabolic pathways for enhanced production. While research into these traditional approaches continues, limitations such as scale-up and time cost hold them back from wider use, while at the same time there is a shift to more novel methods, such as moving from episomal expression to chromosomal integration. Recently, nontraditional approaches such as co-culture systems and cell-free metabolic engineering (CFME) are being investigated for modular optimization. Co-culture modularity looks to optimally divide the metabolic burden between different hosts. CFME seeks to modularly optimize metabolic pathways <i>in vitro</i>, both speeding up the design of such systems and eliminating the issues associated with live hosts. In this review we will examine both traditional and nontraditional approaches for modular optimization, examining recent developments and discussing issues and emerging solutions for future research in metabolic engineering.</p>","PeriodicalId":10794,"journal":{"name":"Critical Reviews in Biochemistry and Molecular Biology","volume":" ","pages":"587-602"},"PeriodicalIF":6.5,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/10409238.2021.1937928","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39135213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 4
Biosynthesis and trafficking of heme o and heme a: new structural insights and their implications for reaction mechanisms and prenylated heme transfer. 血红素o和血红素a的生物合成和运输:新的结构见解及其对反应机制和丙烯化血红素转移的影响。
IF 6.5 2区 生物学
Critical Reviews in Biochemistry and Molecular Biology Pub Date : 2021-12-01 Epub Date: 2021-08-25 DOI: 10.1080/10409238.2021.1957668
Elise D Rivett, Lim Heo, Michael Feig, Eric L Hegg
{"title":"Biosynthesis and trafficking of heme <i>o</i> and heme <i>a</i>: new structural insights and their implications for reaction mechanisms and prenylated heme transfer.","authors":"Elise D Rivett,&nbsp;Lim Heo,&nbsp;Michael Feig,&nbsp;Eric L Hegg","doi":"10.1080/10409238.2021.1957668","DOIUrl":"https://doi.org/10.1080/10409238.2021.1957668","url":null,"abstract":"<p><p>Aerobic respiration is a key energy-producing pathway in many prokaryotes and virtually all eukaryotes. The final step of aerobic respiration is most commonly catalyzed by heme-copper oxidases embedded in the cytoplasmic or mitochondrial membrane. The majority of these terminal oxidases contain a prenylated heme (typically heme <i>a</i> or occasionally heme <i>o</i>) in the active site. In addition, many heme-copper oxidases, including mitochondrial cytochrome <i>c</i> oxidases, possess a second heme <i>a</i> cofactor. Despite the critical role of heme <i>a</i> in the electron transport chain, the details of the mechanism by which heme <i>b</i>, the prototypical cellular heme, is converted to heme <i>o</i> and then to heme <i>a</i> remain poorly understood. Recent structural investigations, however, have helped clarify some elements of heme <i>a</i> biosynthesis. In this review, we discuss the insight gained from these advances. In particular, we present a new structural model of heme <i>o</i> synthase (HOS) based on distance restraints from inferred coevolutionary relationships and refined by molecular dynamics simulations that are in good agreement with the experimentally determined structures of HOS homologs. We also analyze the two structures of heme <i>a</i> synthase (HAS) that have recently been solved by other groups. For both HOS and HAS, we discuss the proposed catalytic mechanisms and highlight how new insights into the heme-binding site locations shed light on previously obtained biochemical data. Finally, we explore the implications of the new structural data in the broader context of heme trafficking in the heme <i>a</i> biosynthetic pathway and heme-copper oxidase assembly.</p>","PeriodicalId":10794,"journal":{"name":"Critical Reviews in Biochemistry and Molecular Biology","volume":" ","pages":"640-668"},"PeriodicalIF":6.5,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8877297/pdf/nihms-1780368.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39340835","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 5
Cancer cells dysregulate PI3K/AKT/mTOR pathway activation to ensure their survival and proliferation: mimicking them is a smart strategy of gammaherpesviruses. 癌细胞失调PI3K/AKT/mTOR通路激活以确保其存活和增殖:模仿它们是γ疱疹病毒的一种聪明策略。
IF 6.5 2区 生物学
Critical Reviews in Biochemistry and Molecular Biology Pub Date : 2021-10-01 Epub Date: 2021-06-15 DOI: 10.1080/10409238.2021.1934811
Mara Cirone
{"title":"Cancer cells dysregulate PI3K/AKT/mTOR pathway activation to ensure their survival and proliferation: mimicking them is a smart strategy of gammaherpesviruses.","authors":"Mara Cirone","doi":"10.1080/10409238.2021.1934811","DOIUrl":"https://doi.org/10.1080/10409238.2021.1934811","url":null,"abstract":"<p><p>The serine/threonine kinase mammalian target of rapamycin (mTOR) is the catalytic subunit of two complexes, mTORC1 and mTORC2, which have common and distinct subunits that mediate separate and overlapping functions. mTORC1 is activated by plenty of nutrients, and the two complexes can be activated by PI3K signaling. mTORC2 acts as an upstream regulator of AKT, and mTORC1 acts as a downstream effector. mTOR signaling integrates both intracellular and extracellular signals, acting as a key regulator of cellular metabolism, growth, and survival. A dysregulated activation of mTOR, as result of PI3K pathway or mTOR regulatory protein mutations or even due to the presence of cellular or viral oncogenes, is a common finding in cancer and represents a central mechanism in cancerogenesis. In the final part of this review, we will focus on the PI3K/AKT/mTOR activation by the human gammaherpesviruses EBV and KSHV that hijack this pathway to promote their-mediated oncogenic transformation and pathologies.</p>","PeriodicalId":10794,"journal":{"name":"Critical Reviews in Biochemistry and Molecular Biology","volume":" ","pages":"500-509"},"PeriodicalIF":6.5,"publicationDate":"2021-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/10409238.2021.1934811","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39233523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 16
Mechanisms linking endoplasmic reticulum (ER) stress and microRNAs to adipose tissue dysfunction in obesity. 肥胖症中内质网应激和microrna与脂肪组织功能障碍的联系机制
IF 6.5 2区 生物学
Critical Reviews in Biochemistry and Molecular Biology Pub Date : 2021-10-01 Epub Date: 2021-06-28 DOI: 10.1080/10409238.2021.1925219
Kalhara R Menikdiwela, João Pedro Tôrres Guimarães, Latha Ramalingam, Nishan S Kalupahana, Jannette M Dufour, Rachel L Washburn, Naima Moustaid-Moussa
{"title":"Mechanisms linking endoplasmic reticulum (ER) stress and microRNAs to adipose tissue dysfunction in obesity.","authors":"Kalhara R Menikdiwela,&nbsp;João Pedro Tôrres Guimarães,&nbsp;Latha Ramalingam,&nbsp;Nishan S Kalupahana,&nbsp;Jannette M Dufour,&nbsp;Rachel L Washburn,&nbsp;Naima Moustaid-Moussa","doi":"10.1080/10409238.2021.1925219","DOIUrl":"https://doi.org/10.1080/10409238.2021.1925219","url":null,"abstract":"<p><p>Over accumulation of lipids in adipose tissue disrupts metabolic homeostasis by affecting cellular processes. Endoplasmic reticulum (ER) stress is one such process affected by obesity. Biochemical and physiological alterations in adipose tissue due to obesity interfere with adipose ER functions causing ER stress. This is in line with increased irregularities in other cellular processes such as inflammation and autophagy, affecting overall metabolic integrity within adipocytes. Additionally, microRNAs (miRNAs), which can post-transcriptionally regulate genes, are differentially modulated in obesity. A better understanding and identification of such miRNAs could be used as novel therapeutic targets to fight against diseases. In this review, we discuss ways in which ER stress participates as a common molecular process in the pathogenesis of obesity-associated metabolic disorders. Moreover, our review discusses detailed underlying mechanisms through which ER stress and miRNAs contribute to metabolic alteration in adipose tissue in obesity. Hence, identifying mechanistic involvement of miRNAs-ER stress cross-talk in regulating adipose function during obesity could be used as a potential therapeutic approach to combat chronic diseases, including obesity.</p>","PeriodicalId":10794,"journal":{"name":"Critical Reviews in Biochemistry and Molecular Biology","volume":" ","pages":"455-481"},"PeriodicalIF":6.5,"publicationDate":"2021-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/10409238.2021.1925219","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39137685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 15
Cellular mechanisms of mtDNA heteroplasmy dynamics. 线粒体dna异质性动力学的细胞机制。
IF 6.5 2区 生物学
Critical Reviews in Biochemistry and Molecular Biology Pub Date : 2021-10-01 DOI: 10.1080/10409238.2021.1934812
Claudia V Pereira, Bryan L Gitschlag, Maulik R Patel
{"title":"Cellular mechanisms of mtDNA heteroplasmy dynamics.","authors":"Claudia V Pereira,&nbsp;Bryan L Gitschlag,&nbsp;Maulik R Patel","doi":"10.1080/10409238.2021.1934812","DOIUrl":"https://doi.org/10.1080/10409238.2021.1934812","url":null,"abstract":"<p><p>Heteroplasmy refers to the coexistence of more than one variant of the mitochondrial genome (mtDNA). Mutated or partially deleted mtDNAs can induce chronic metabolic impairment and cause mitochondrial diseases when their heteroplasmy levels exceed a critical threshold. These mutant mtDNAs can be maternally inherited or can arise <i>de novo</i>. Compelling evidence has emerged showing that mutant mtDNA levels can vary and change in a nonrandom fashion across generations and amongst tissues of an individual. However, our lack of understanding of the basic cellular and molecular mechanisms of mtDNA heteroplasmy dynamics has made it difficult to predict who will inherit or develop mtDNA-associated diseases. More recently, with the advances in technology and the establishment of tractable model systems, insights into the mechanisms underlying the selection forces that modulate heteroplasmy dynamics are beginning to emerge. In this review, we summarize evidence from different organisms, showing that mutant mtDNA can experience both positive and negative selection. We also review the recently identified mechanisms that modulate heteroplasmy dynamics. Taken together, this is an opportune time to survey the literature and to identify key cellular pathways that can be targeted to develop therapies for diseases caused by heteroplasmic mtDNA mutations.</p>","PeriodicalId":10794,"journal":{"name":"Critical Reviews in Biochemistry and Molecular Biology","volume":"56 5","pages":"510-525"},"PeriodicalIF":6.5,"publicationDate":"2021-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/10409238.2021.1934812","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10118076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 17
The amyloid proteome: a systematic review and proposal of a protein classification system. 淀粉样蛋白组:一种蛋白质分类系统的综述和建议。
IF 6.5 2区 生物学
Critical Reviews in Biochemistry and Molecular Biology Pub Date : 2021-10-01 Epub Date: 2021-07-27 DOI: 10.1080/10409238.2021.1937926
Juliane Gottwald, Christoph Röcken
{"title":"The amyloid proteome: a systematic review and proposal of a protein classification system.","authors":"Juliane Gottwald,&nbsp;Christoph Röcken","doi":"10.1080/10409238.2021.1937926","DOIUrl":"https://doi.org/10.1080/10409238.2021.1937926","url":null,"abstract":"<p><p>Amyloidosis is a disease caused by pathological fibril aggregation and deposition of proteins in different tissues and organs. Thirty-six fibril-forming proteins have been identified. So far, proteomic evaluation of amyloid focused on the detection and characterization of fibril proteins mainly for diagnostic purposes or to find novel fibril-forming proteins. However, amyloid deposits are a complex mixture of constituents that show organ-, tissue-, and amyloid-type specific patterns, that is the amyloid proteome. We carried out a comprehensive literature review on publications investigating amyloid via liquid chromatography coupled to tandem mass spectrometry, including but not limited to sample preparation by laser microdissection. Our review confirms the complexity and dynamics of the amyloid proteome, which can be divided into four functional categories: amyloid proteome-category 1 (APC1) includes exclusively fibrillary proteins found in the patient; APC2 includes potential fibril-forming proteins found in other types of amyloid; and APC3 and APC4 summarizes non-fibril proteins-some being amyloid signature proteins. Our categorization may help to systemically explore the nature and role of the amyloid proteome in the manifestation, progression, and clearance of disease. Further exploration of the amyloid proteome may form the basis for the development of novel diagnostic tools, thereby enabling the development of novel therapeutic targets.</p>","PeriodicalId":10794,"journal":{"name":"Critical Reviews in Biochemistry and Molecular Biology","volume":" ","pages":"526-542"},"PeriodicalIF":6.5,"publicationDate":"2021-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/10409238.2021.1937926","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39224001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 7
Novel insights into the mechanism of cell cycle kinases Mec1(ATR) and Tel1(ATM). 细胞周期激酶Mec1(ATR)和Tel1(ATM)机制的新见解。
IF 6.5 2区 生物学
Critical Reviews in Biochemistry and Molecular Biology Pub Date : 2021-10-01 Epub Date: 2021-06-20 DOI: 10.1080/10409238.2021.1925218
Elias A Tannous, Peter M Burgers
{"title":"Novel insights into the mechanism of cell cycle kinases Mec1(ATR) and Tel1(ATM).","authors":"Elias A Tannous,&nbsp;Peter M Burgers","doi":"10.1080/10409238.2021.1925218","DOIUrl":"https://doi.org/10.1080/10409238.2021.1925218","url":null,"abstract":"<p><p>DNA replication is a highly precise process which usually functions in a perfect rhythm with cell cycle progression. However, cells are constantly faced with various kinds of obstacles such as blocks in DNA replication, lack of availability of precursors and improper chromosome alignment. When these problems are not addressed, they may lead to chromosome instability and the accumulation of mutations, and even cell death. Therefore, the cell has developed response mechanisms to keep most of these situations under control. Of the many factors that participate in this DNA damage response, members of the family of phosphatidylinositol 3-kinase-related protein kinases (PIKKs) orchestrate the response landscape. Our understanding of two members of the PIKK family, human ATR (yeast Mec1) and ATM (yeast Tel1), and their associated partner proteins, has shown substantial progress through recent biochemical and structural studies. Emerging structural information of these unique kinases show common features that reveal the mechanism of kinase activity.</p>","PeriodicalId":10794,"journal":{"name":"Critical Reviews in Biochemistry and Molecular Biology","volume":" ","pages":"441-454"},"PeriodicalIF":6.5,"publicationDate":"2021-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/10409238.2021.1925218","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39251358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 6
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